Utilization of three-dimensional cyclic scaffolds is important in modern drug discovery, both to provide greater opportunities for optimizing drug candidates and to expand the available chemical space of drugs. Among these scaffolds, bicyclo[1.1.1]pentane (BCP) is a high-value bioisostere for 1,4-disubstituted phenyl rings, internal alkynes, and the tert-butyl group, generally offering high passive permeability, high water solubility, and improved metabolic stability. However, the lack of methods for functionalizing BCP remains a significant challenge, and in particular, a versatile strategy for synthesizing a wide range of unsymmetrically 1,3-difunctionalized BCP derivatives has been lacking. In this account, we review recent advances in the synthetic chemistry of BCP, focusing especially on our recently developed radical multicomponent carboamination of [1.1.1]propellane. 1 Introduction 2 Overview of the Synthetic Chemistry of [1.1.1]Propellane, the Most Promising Precursor of Bicyclo[1.1.1]pentane 3 Recent Advances in the Synthetic Chemistry of Unsymmetrically 1,3-Disubstituted Bicyclo[1.1.1]pentane Derivatives 4 Radical Multicomponent Carboamination of [1.1.1]Propellane Permits Direct Synthesis of 3-Substituted Bicyclo[1.1.1]pent-1-ylamine Derivatives 5 Conclusion

中文翻译：

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双环[1.1.1]戊烷合成化学新进展

三维环状支架的利用在现代药物发现中很重要，既可以为优化候选药物提供更多机会，也可以扩大药物的可用化学空间。在这些支架中，双环 [1.1.1] 戊烷 (BCP) 是 1,4-二取代苯环、内部炔烃和叔丁基的高价值生物电子等排体，通常具有高被动渗透性、高水溶性和提高代谢稳定性。然而，缺乏功能化 BCP 的方法仍然是一个重大挑战，特别是缺乏合成各种不对称 1,3-双功能化 BCP 衍生物的通用策略。在这个帐户中，我们回顾了 BCP 合成化学的最新进展，特别关注我们最近开发的 [1.1.1] 丙烷的自由基多组分碳胺化。1 引言 2 [1.1.1] 丙烷（双环[1.1.1] 戊烷最有前途的前体）合成化学概述 3 不对称 1,3-二取代双环 [1.1.1] 戊烷衍生物合成化学的最新进展4 [1.1.1] 丙烷的自由基多组分碳胺化允许直接合成 3-取代的双环 [1.1.1]pent-1-ylamine 衍生物 5 结论